TY - JOUR
T1 - Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress
AU - Varzideh, Fahimeh
AU - Jankauskas, Stanislovas S.
AU - Kansakar, Urna
AU - Mone, Pasquale
AU - Gambardella, Jessica
AU - Santulli, Gaetano
N1 - Publisher Copyright:
© 2022, Varzideh et al.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders.
AB - Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders.
UR - http://www.scopus.com/inward/record.url?scp=85124059480&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124059480&partnerID=8YFLogxK
U2 - 10.1172/JCI156624
DO - 10.1172/JCI156624
M3 - Review article
C2 - 35104807
AN - SCOPUS:85124059480
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
M1 - e156624
ER -